John Burke's Smoking Behavior
"Once someone starts smoking, genetics have a large effect on how much she smokes and how hard it will be to quit."-23 and Me. Introduction: According to 23andMe there is a single, and highly heritable genotype that several studies identified to affect a person's propensity to continue smoking, and for John Burke this may explain much, or not. In short, the allele varieties have only been identified to have potential affects after ''someone has already started smoking. The first genotype is GG, which has been associated with European smokers who smoke the typical amount of cigarettes per day compared to the typical European smoker. This means that this genotype does not seem to have any effect to increase the number of cigarettes smoked per day in European smokers. The other homozygous alternative is AA: which is associated with an increase of 2 more cigarettes per day in Europeans with this genotype compared to the typical amount of cigarettes smoked per day by European smokers.. The heterozygous genotype is AG: This genotype is associated with an increase of 1 more cigarette per day in Europeans with this genotype compared to the typical amount of cigarettes smoked per day by Europeans23andMe: https://www.23andme.com/you/journal/smokingbehavior/overview/. Professor Burke, a modest man of moderation, has the AG genotype, and therefore the propensity to smoke just one more cigarette. '''What is the 23andMe Gene?' 23andMe chose to test for genotypes of a specific gene called CHRNA3, which is part of the CHRNA gene family. The CHRNA3 gene has SNPs which are strongly associated with the propensity to smoke more cigarettes (see above) and encodes for a part of one kind of nicotine receptor. The Environment and Smoking: First and foremost, it is important to note that the genotype tested by 23andMe and the studies cited by 23andMe, which associate these SNPs with smoking behavior, have not claimed to have associations between a genotype and a propensity to smoke, or start smoking. The effect these genotypes may have on the number of cigarettes someone smokes per day are only after they have started smoking, and were only studied in a European population. The Whole Picture of Genomics and Smoking: There are several genes associated with smoking that 23andMe did not test. One gene is a variant of the BDNF gene, and is associated with an increased risk of starting to smoke. Also, within the CHRNA gene family there are 2 other critical smoking genes that 23andMe did not test. One is PPP1R3C, which has variants associated with an increase in the number of cigarettes smoked per day. Another is CYP2A6, which has variants associated both with an increase in the number of cigarettes smoked per day and an increased risk in lung cancer developmentAmos, CL et al.,2010, Chipping away at the genetics of smoking behavior, Nature Genetics, http://www.ncbi.nlm.nih.gov/pubmed/20428092. Amos, CL et al.,2010, Chipping away at the genetics of smoking behavior, Nature Genetics, http://www.ncbi.nlm.nih.gov/pubmed/20428092 Getting Into Some Specific Research'''Amos, CL et al.,2010, Chipping away at the genetics of smoking behavior, Nature Genetics, http://www.ncbi.nlm.nih.gov/pubmed/20428092:' So, to summarize the 23andMe report, each copy of the A allele was associated with one more cigarette per day in European smokers. However, it has also been found that each copy of A is associated with an increase in blood soluble nicotine concentrations, which is an indicator of nicotine exposure. Based on data from 23andMe, the company has hypothesized that this increase may be a result of deeper inhalation or smoking more of each cigarette. Professor Burke will surely be able to provide a personal anecdote on this matter. In a study of 45,691 smokers using samples from the Tobacco and Genetics (TAG) study and the Glaxo-Smith Kline (Ox-GSK) study it was found that 3 genetic loci had important associations. The first locus is on chromosome 15 and was identified as having associations with an increase in cigarettes smoked per day, 1 genetic locus on chromosome 8 and another on chromosome 19 were both identified as having strong associations with a slight increase risk for lung cancer. Chromosome 15:The specific location is 15q25 rs1051730. The A variant was found to have an effect size of 0.80 more cigarettes per day (P=2.4E-69), Chromosome 8: The specific location is 8p11 rs6474412. The T variant had an effect size of 0.29 more cigarettes per day (P=1.4E-8). Chromosome 19: The specific location is 19q13 rs4105144. The C variant had an effect size of 0.39 more cigarettes per day (P=2.2E-12). '''References:'